Bottom Line:
We identified and optimized various formulations and process parameters to get the preferred particle size, entrapment, and polydispersibility of the VEGF-NPs, and incorporated the VEGF-NPs into the (poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (Pluronic®) F127 to achieve the preferred VEGF-NPs thermo-sensitive gel system.Furthermore, the system can create a satisfactory tissue-compatible environment and an effective VEGF-sustained release approach.In conclusion, a novel VEGF-loaded PLGA NPs-embedded thermo-sensitive hydrogel in porcine BAMA system is successfully prepared, to provide a promising way for deficient bladder reconstruction therapy.

ABSTRACTWe fabricated a novel vascular endothelial growth factor (VEGF)-loaded poly(lactic-co-glycolic acid) (PLGA)-nanoparticles (NPs)-embedded thermo-sensitive hydrogel in porcine bladder acellular matrix allograft (BAMA) system, which is designed for achieving a sustained release of VEGF protein, and embedding the protein carrier into the BAMA. We identified and optimized various formulations and process parameters to get the preferred particle size, entrapment, and polydispersibility of the VEGF-NPs, and incorporated the VEGF-NPs into the (poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (Pluronic®) F127 to achieve the preferred VEGF-NPs thermo-sensitive gel system. Then the thermal behavior of the system was proven by in vitro and in vivo study, and the kinetic-sustained release profile of the system embedded in porcine bladder acellular matrix was investigated. Results indicated that the bioactivity of the encapsulated VEGF released from the NPs was reserved, and the VEGF-NPs thermo-sensitive gel system can achieve sol-gel transmission successfully at appropriate temperature. Furthermore, the system can create a satisfactory tissue-compatible environment and an effective VEGF-sustained release approach. In conclusion, a novel VEGF-loaded PLGA NPs-embedded thermo-sensitive hydrogel in porcine BAMA system is successfully prepared, to provide a promising way for deficient bladder reconstruction therapy.

Mentions:
It is noteworthy to mention again that an appropriate sol-gel temperature, gelation, and maintaining of its consistency after injection of the block copolymer solution, were crucial for its utilization for various applications. Tube inversion has been used previously by several groups to determine the gel boundary of gel-sol behavior [23]. Thermoreversible sol-gel transition of F127 aqueous solution originates from micelle formation and micelle volume change owing to PEO/water, and PPO/water's lower critical solution temperature (LCST) behavior [24]. Above LCST temperature of PPO, the micelle with PPO core and PEO shell appears. As temperature increases, the number of micelles increases. At high temperature, interaction of PEO and water is unfavorable, and therefore, gel-to-sol transition occurs because of dehydration and shrinking of PEO shell. Above PEO-water LCST temperature, phase separation between polymer and water is observed. As illustrated in Figure 3, gelation temperature decreased with increase of the concentration of F127 and decreased proportionally to the concentration. Solutions containing less than 15.4% F127 did not form gels over the tested temperature range, while a F127 concentration higher than 30% led to difficulty in preparation and administration. In this study, approximately 25% of F127 was required to obtain NPs hydrogel formulation with the transition temperature of approx. 20°C (Figure 4a, b).

Mentions:
It is noteworthy to mention again that an appropriate sol-gel temperature, gelation, and maintaining of its consistency after injection of the block copolymer solution, were crucial for its utilization for various applications. Tube inversion has been used previously by several groups to determine the gel boundary of gel-sol behavior [23]. Thermoreversible sol-gel transition of F127 aqueous solution originates from micelle formation and micelle volume change owing to PEO/water, and PPO/water's lower critical solution temperature (LCST) behavior [24]. Above LCST temperature of PPO, the micelle with PPO core and PEO shell appears. As temperature increases, the number of micelles increases. At high temperature, interaction of PEO and water is unfavorable, and therefore, gel-to-sol transition occurs because of dehydration and shrinking of PEO shell. Above PEO-water LCST temperature, phase separation between polymer and water is observed. As illustrated in Figure 3, gelation temperature decreased with increase of the concentration of F127 and decreased proportionally to the concentration. Solutions containing less than 15.4% F127 did not form gels over the tested temperature range, while a F127 concentration higher than 30% led to difficulty in preparation and administration. In this study, approximately 25% of F127 was required to obtain NPs hydrogel formulation with the transition temperature of approx. 20°C (Figure 4a, b).

Bottom Line:
We identified and optimized various formulations and process parameters to get the preferred particle size, entrapment, and polydispersibility of the VEGF-NPs, and incorporated the VEGF-NPs into the (poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (Pluronic®) F127 to achieve the preferred VEGF-NPs thermo-sensitive gel system.Furthermore, the system can create a satisfactory tissue-compatible environment and an effective VEGF-sustained release approach.In conclusion, a novel VEGF-loaded PLGA NPs-embedded thermo-sensitive hydrogel in porcine BAMA system is successfully prepared, to provide a promising way for deficient bladder reconstruction therapy.

ABSTRACTWe fabricated a novel vascular endothelial growth factor (VEGF)-loaded poly(lactic-co-glycolic acid) (PLGA)-nanoparticles (NPs)-embedded thermo-sensitive hydrogel in porcine bladder acellular matrix allograft (BAMA) system, which is designed for achieving a sustained release of VEGF protein, and embedding the protein carrier into the BAMA. We identified and optimized various formulations and process parameters to get the preferred particle size, entrapment, and polydispersibility of the VEGF-NPs, and incorporated the VEGF-NPs into the (poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (Pluronic®) F127 to achieve the preferred VEGF-NPs thermo-sensitive gel system. Then the thermal behavior of the system was proven by in vitro and in vivo study, and the kinetic-sustained release profile of the system embedded in porcine bladder acellular matrix was investigated. Results indicated that the bioactivity of the encapsulated VEGF released from the NPs was reserved, and the VEGF-NPs thermo-sensitive gel system can achieve sol-gel transmission successfully at appropriate temperature. Furthermore, the system can create a satisfactory tissue-compatible environment and an effective VEGF-sustained release approach. In conclusion, a novel VEGF-loaded PLGA NPs-embedded thermo-sensitive hydrogel in porcine BAMA system is successfully prepared, to provide a promising way for deficient bladder reconstruction therapy.